Berkeley researchers have identified a new enzyme that plays a major role in controlling the breakdown of fat in mice. The study is published in the January 11 edition of the journal Nature Medicine.

Hei Sook Sul, professor of nutritional sciences and toxicology at UC Berkeley and principal investigator of the research said, "we have discovered a new enzyme within fat cells that is a key regulator of fat metabolism and body weight, making it a promising target in the search for a treatment for human obesity."

Sul's research team includes the three co-lead authors of the paper, all from UC Berkeley's Department of Nutritional Sciences and Toxicology: Kathy Jaworski, former post-doctoral researcher; Maryam Ahmadian, graduate student; and Robin Duncan, post-doctoral fellow.

The enzyme in the spotlight, adipose-specific phospholipase A2 (AdPLA), is found in abundance only in fat tissue. AdPLA sets off a chain of events that increases levels of a signaling molecule called prostaglandin E2 (PGE2), which suppresses the breakdown of fat. Mice that have no AdPLA have lower PGE2 levels and a higher rate of fat metabolism.

"When levels of PGE2 are decreased because of the lack of AdPLA, fat breakdown proceeds unchecked, resulting in leanness even in animals that eat all day long," said co-lead author Duncan.

Before this paper, the assumption had been that the major players in controlling fat metabolism and body weight were endocrine factors, primarily hormones that are secreted by different organs and glands and travel through the bloodstream to fat tissue, the authors said.

The new findings show that a large portion of the action is occurring within the actual fat tissue, mainly through the autocrine and paracrine action of PGE2 that acts locally within a cell or small group of cells.